Lean electrolyte for biocompatible plasmaelectrolytic coatings on magnesium implant material

ABSTRACT

The present disclosure is directed, at least in part, to a method of producing ceramic layers on magnesium and its alloys, a magnesium implant with a ceramic layer made by the method, and a magnesium implant having a biocompatible ceramic layer substantially free of material which impairs the biocompatibility of said biocompatible ceramic layer. In an exemplary embodiment, the method of producing ceramic layers on magnesium and its alloys, includes (a) immersing an implant and a metal sheet into the aqueous electrolyte bath, said aqueous electrolyte bath including: ammoniac, diammonium hydrogen phosphate and urea, and wherein the implant is made of magnesium or its alloy; (b) performing a anodic oxidation by passing a current between the implant, the metal sheet and through the aqueous electrolyte bath, wherein the implant is connected to a positive pole of a current source and the metal sheet is connected to a negative pole of the current source; (c) applying a current density selected to form sparks on said implant, to thereby form a ceramic layer on said implant.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional PatentApplication No. 61/556,563, filed Nov. 7, 2011, which is incorporatedherein by reference in its entirety.

FIELD OF THE INVENTION

The present disclosure is directed, at least in part, to a method ofproducing ceramic layers on magnesium and its alloys, a magnesiumimplant with a ceramic layer made by the method, and a magnesium implanthaving a biocompatible ceramic layer substantially free of materialwhich impairs the biocompatibility of said biocompatible ceramic layer.

BACKGROUND OF THE INVENTION

Traditional methods of osteosynthesis and osteotomy used permanent metalimplants made of steel or titanium. However, since these durable metalimplants represent a foreign body, patients receiving them arepotentially at a greater risk of a local inflammation. Moreover, whilethese implants tend to permanently protect healing bones againstmechanical exposure, this stress shielding-effect actually forestallsthe stabilization of the bone tissue that needs mechanical loads toobtain and maintain its rigidity. One solution to this problem requiresa follow up surgery to remove the permanent metal implants. But suchfollow up surgeries increase the risk of re-fracture of the healingbones, and/or cause the patients to suffer unnecessary inconveniences,including delayed recovery and incurrence of additional expenses.

Alternative implants using metallic magnesium and certain magnesiumalloys have been shown to be biodegradable and potentially suitable formedical applications. However, because of the electrochemical activityof magnesium, the corrosion rates of such implants are highly dependenton factors such as implant composition, type of environment or site ofimplantation, and the surface condition of the implant (treated oruntreated). When exposed to air the surface of untreated magnesiumimplants reacts with oxygen, building up a layer of magnesium hydroxideon the surface, thereby slowing down further chemical reactions. Insaline media, such as in the environment of the human organism,untreated magnesium implants initially corrode very rapidly, producinghigh amounts of hydrogen gas and magnesium hydroxide. Uncontrolledcorrosion of magnesium implants can cause premature failure of loadedimplants due to stress corrosion cracking and/or due to corrosionfatigue. Moreover, because of the initial high gas release subcutaneousgas cavities might form. Thus, a need exists for magnesium basedimplants with improved corrosion performance.

The initial high gas release and the formation of gas bubbles in vivocan potentially be avoided by application of a coating to the surface ofthe magnesium implants prior to implantation. The coating would retardthe rate of corrosion of the metal implants, thereby stabilizing therate of gas release due to corrosion of the implants. Several attemptsto improve corrosion performance of magnesium have been reported,including coating by anodization in solutions of concentrated alkalinehydroxides, or in solutions of hydrofluoric acid or acid fluoride salts.

Anodization of magnesium using base solutions of concentrated alkalinehydroxides is generally provided through the supply of a DC current at arange of 50 volts to 150 volts. A coating is formed on the magnesiumthrough the formation of sparks within the bath. The tracking of thesparks across the surface of the magnesium element slowly places thecoating onto the magnesium. The use of sparks throughout the processleads to a relatively high current usage and to significant heatabsorption by the bath itself. Therefore, cooling may be necessary toreduce the temperature of the bath during the anodization process.

Use of hydrofluoric acid or acid fluoride salts in anodization ofmagnesium results in the formation of a protective layer of magnesiumfluoride on the magnesium surface. This protective layer is not solublein water and thus prevents further reaction of the magnesium metal.

Other methods for anodization of magnesium or alloys of magnesiumincorporate other species into the film as it is formed on the surfaceof the magnesium. Some anodization processes use silicates and othersuse various ceramic materials.

However, many of the reported magnesium coatings might be toxic.Therefore, a need exists for biocompatible coating compositions andcoating processes will produce resorbable biomaterial onto the surfaceof magnesium implants that cannot completely prevent the degradationprocess, so the performance of the implants can be modulated by how theimplant is coated and/or the corrosion characteristic of the basematerial used to coat the implants.

BRIEF SUMMARY OF THE INVENTION

An aspect of the present disclosure provides for a method of producingceramic layers on magnesium and its alloys. An exemplary method inaccordance with the present invention comprises the steps of: (a)immersing an implant and a metal sheet into the aqueous electrolytebath, said aqueous electrolyte bath consisting essentially of: ammoniac(NH₃), diammonium hydrogen phosphate ((NH₄)₂HPO₄) and urea (CH₄N₂O), andwherein the implant is made of magnesium or its alloy; (b) performing aanodic oxidation by passing a current between the implant, the metalsheet and through the aqueous electrolyte bath, wherein the implant isconnected to a positive pole of a current source and the metal sheet isconnected to a negative pole of the current source; (c) applying acurrent density selected to form sparks on said implant, to thereby forma ceramic layer on said implant. In an embodiment, the ammoniacconcentration at 25 vol. % ranges from 1.0 mol/L to 6.0 mol/L, thediammonium hydrogen phosphate concentration ranges from 0.05 mol/L to0.2 mol/L; and the urea concentration ranges from 0.01 mol/L to 1.0mol/L.

Another exemplary method in accordance with the present inventioncomprises the steps of: (a) immersing an implant and a metal sheet intothe aqueous electrolyte bath, said aqueous electrolyte bath consistingof: ammoniac, diammonium hydrogen phosphate and urea, and wherein theimplant is made of magnesium or its alloy; (b) performing a anodicoxidation by passing a current between the implant, the metal sheet andthrough the aqueous electrolyte bath, wherein the implant is connectedto a positive pole of a current source and the metal sheet is connectedto a negative pole of the current source; (c) applying a current densityselected to form sparks on said implant, to thereby form a ceramic layeron said implant. In an embodiment, the ammoniac concentration at 25 vol.% ranges from 1.0 mol/L to 6.0 mol/L, the diammonium hydrogen phosphateconcentration ranges from 0.05 mol/L to 0.2 mol/L; and the ureaconcentration ranges from 0.01 mol/L to 1.0 mol/L.

In an embodiment, the aqueous electrolyte bath has a pH value rangingfrom 10.3 to 11.6 and a temperature ranging from 18° C. to 22° C. Inanother embodiment, the current density is at least 1 A/dm². In anotherembodiment, the current density ranges from 1 A/dm² to 3 A/dm². In yetanother embodiment, the coating is selectively applied to the implant byelectrically insulating areas of the surface which are not to be coated.In another embodiment, electric insulation of the areas which are not tobe coated is achieved by applying a lacquer, film or foil or the likewhich can be removed after the coating process (e.g. by manualdelamination).

Another aspect of the present disclosure provides for a magnesiumimplant with a ceramic layer made by exemplary methods according to thepresent invention. In an exemplary embodiment of said magnesium implantwith a ceramic layer, said layer is an oxide, hydroxide or phosphateceramic layer or a combination thereof and has a thickness of up to 50μm. In another embodiment of the magnesium implant with a ceramic layer,said ceramic layer has a thickness ranging from 2 μm to 20 μm. Inanother embodiment of the magnesium implant with a ceramic layer, saidceramic layer selected from the group consisting of: MgO, Mg(OH)₂,Mg₃(PO₄)₂ and oxides of alloying elements of magnesium. In yet anotherembodiment of the magnesium implant with a ceramic layer, said ceramiclayer improves bone tissue adhesion compared to non-coated magnesiumimplant and is substantially free of substances which impairbiocompatibility. In an embodiment of the magnesium implant with aceramic layer, said magnesium implant is substantially free ofsubstances which impair biocompatibility. In one such embodiment, saidsubstances comprise an amine decomposition product.

According to another exemplary embodiment of the magnesium implant ofthe present invention, said magnesium implant has a biocompatibleceramic layer substantially free of material which impairs thebiocompatibility of said biocompatible ceramic layer, said biocompatibleceramic layer having a thickness of up to 50 μm. In one embodiment, saidbiocompatible ceramic layer includes a component selected from the groupconsisting of MgO, Mg(OH)₂, Mg₃(PO₄)₂, oxides of alloying elements ofmagnesium and combinations thereof. In one such embodiment, saidmaterial which impairs the biocompatibility of said biocompatibleceramic layer comprises an amine decomposition product.

In an embodiment of the magnesium implant with a ceramic layer, saidimplant delays and reduces hydrogen release, compared to a magnesiumimplant without said biocompatible oxide ceramic layer, when immersed ina simulated body fluid. In yet another embodiment of the magnesiumimplant with a ceramic layer, said hydrogen release is reduced withrespect to the corroded mass of magnesium compared to a magnesiumimplant without said ceramic layer by 10% to 50% over an immersionperiod of up to 40 days.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing summary, as well as the following detailed description ofthe invention, will be better understood when read in conjunction withthe appended drawings. For the purpose of illustrating the invention,there are shown in the drawings embodiments which are presentlypreferred. It should be understood, however, that the invention can beembodied in different forms and thus should not be construed as beinglimited to the embodiments set forth herein.

FIG. 1 is an SEM image of a coating according to an embodiment of theinvention with coarse pores;

FIG. 2 is an SEM image of a coating according to another embodiment ofthe invention with fine pores;

FIG. 3 illustrates the position of implanted strength retention platesaccording to an embodiment of the invention on a miniature pig nasalbone;

FIG. 4 illustrates a 3-point-bending test of a degraded rectangularplate according to an embodiment of the invention;

FIG. 5 shows average gas release rate of coated and non-coatedrectangular plates according to certain embodiments of the inventionimmersed in simulated body fluid (SBF) for up to 12 weeks (average of 6tests per data point);

FIG. 6 shows gas release as a function of weight loss of coated andnon-coated rectangular plates according to certain embodiments of theinvention immersed in SBF for up to 12 weeks (average of 6 tests perdata point);

FIG. 7 shows an X-ray image of a non-coated magnesium plate according toan embodiment of the invention implanted in a miniature pig after 1week;

FIG. 8 shows an X-ray image of a coated magnesium plate according to anembodiment of the invention implanted in a miniature pig beforeeuthanasia at 12 weeks;

FIG. 9 shows decrease of yield strength for in vitro and in vivodegraded rectangular plates according to certain embodiments of theinvention;

FIG. 10 shows in vitro degradation behavior of non-coated WE43 magnesiumalloy samples and WE43 magnesium alloy samples coated according tocertain embodiments of the invention, during immersion in simulated bodyfluid (SBF);

FIG. 11 shows average accumulated gas release of tensioned WE43magnesium alloy samples, treated in accordance with certain embodimentsof the invention, during immersion in SBF;

FIG. 12 shows strength retention (remaining bending force) measurementsof tensioned WE43 magnesium alloy samples, treated in accordance withcertain embodiments of the invention, during immersion in SBF;

FIG. 13 shows failure times as a function of coating variants (6specimens per variant) according to certain embodiments of the inventionon WE43 magnesium alloy samples;

FIG. 14A shows an example WE43 magnesium alloy sample, treated inaccordance with an embodiment of the invention, after plasticdeformation around a 16 mm diameter cylinder;

FIG. 14B shows an example WE43 magnesium alloy sample, treated inaccordance with an embodiment of the invention, after tensioning andpositioning in a sample holder;

FIG. 15A shows an example WE43 magnesium alloy sample, treated inaccordance with an embodiment of the invention, positioned in a holderwith screw fixation for strength retention testing;

FIG. 15B shows an example WE43 magnesium alloy sample, treated inaccordance with an embodiment of the invention, in a holder with screwfixation for strength retention testing prior to immersion in SBF;

FIG. 15C shows the WE43 magnesium alloy sample of FIG. 15B after sixweeks of immersion in SBF;

FIG. 15D shows the WE43 magnesium alloy sample of FIG. 15C after removalfrom the holder;

FIGS. 16A-16D show example bone plate configurations in accordance withsome embodiments of the invention; and

FIGS. 17A and 17B show other example bone plate configurations inaccordance with further embodiments of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The present subject matter will now be described more fully hereinafterwith reference to the accompanying Figures and Examples, in whichrepresentative embodiments are shown. The present subject matter can,however, be embodied in different forms and should not be construed aslimited to the embodiments set forth herein. Rather, these embodimentsare provided to describe and enable one of skill in the art. Unlessotherwise defined, all technical and scientific terms used herein havethe same meaning as commonly understood by one of ordinary skill in theart to which the subject matter pertains. All publications, patentapplications, patents, and other references mentioned herein areincorporated by reference in their entirety.

During the degradation of metallic magnesium implant, hydrogen gas andmagnesium hydroxide are formed by the corrosion reaction. If the amountof released gas surpasses the absorption and diffusion capacity of thesurrounding tissue, gas bubbles might form and are often visible onX-rays. The bare metal surface causes an initial increased release ofgas right after implantation, but soon after the metal surface iscovered with degradation products, the gas release rate stabilizes andmight be low enough to allow sufficient gas transport. The applicationof a coating could avoid the initial high gas release and the formationof gas bubbles. Also, an adequate coating should effectively avoidpremature failure of loaded implants due to stress corrosion crackingand/or corrosion fatigue. Moreover, a coating should be biocompatibleand be obtainable without the use of toxic or potentially harmfulsubstances.

Accordingly, an aspect of the present invention provides a method ofproducing ceramic layers on magnesium and its alloys. In someembodiments of the invention, the method includes exposing a magnesiumor magnesium alloy implant to an aqueous electrolyte comprising,consisting of, or consisting essentially of: ammoniac, diammoniumhydrogen phosphate and urea. In an embodiment, said method comprises (a)immersing an implant and a metal sheet into an aqueous electrolyte bath,said aqueous electrolyte bath consisting essentially of: ammoniac,diammonium hydrogen phosphate and urea, said implant being made ofmagnesium or its alloy; (b) performing an anodic oxidation by passing acurrent between said implant, said metal sheet and through said aqueouselectrolyte bath, wherein said implant is connected to a positive poleof a current source and said metal sheet is connected to a negative poleof said current source; (c) applying a current density selected to formsparks on said implant, to thereby form a ceramic layer on said implant.For the purpose of this application, consisting essentially of shallmean that in addition to the recited components, the aqueous electrolytebath may include other components that do not materially affect thecharacteristics of the ceramic layer of the magnesium implant. In someembodiments, such characteristics may include one or more of bone tissueadhesion of the implant, biocompatibility, absence of aminedecomposition products, and reduced hydrogen gas evolution each comparedto an uncoated magnesium implant.

In an embodiment, the ammoniac concentration at 25 vol. % ranges from1.0 mol/L to 6.0 mol/L. In another embodiment, the diammonium hydrogenphosphate concentration ranges from 0.05 mol/L to 0.2 mol/L. In anotherembodiment the urea concentration ranges from 0.01 mol/L to 1.0 mol/L.In an embodiment, the ammoniac concentration at 25 vol. % ranges from1.0 mol/L to 6.0 of and the diammonium hydrogen phosphate concentrationranges from 0.05 mol/L to 0.2 mol/L. In an embodiment, the ammoniacconcentration at 25 vol. % ranges from 1.0 mol/L to 6.0 of and the ureaconcentration ranges from 0.01 mol/L to 1.0 mol/L. In an embodiment, thediammonium hydrogen phosphate concentration ranges from 0.05 mol/L to0.2 mol/L and the urea concentration ranges from 0.01 mol/L to 1.0mol/L.

In another exemplary embodiment, the present invention provides a methodof producing ceramic layers on magnesium and its alloys, said methodcomprises (a) immersing an implant and a metal sheet into an aqueouselectrolyte bath, said aqueous electrolyte bath consisting of: ammoniac,diammonium hydrogen phosphate and urea, said implant being made ofmagnesium or its alloy; (b) performing an anodic oxidation by passing acurrent between said implant, said metal sheet and through said aqueouselectrolyte bath, wherein said implant is connected to a positive poleof a current source and said metal sheet is connected to a negative poleof said current source; (c) applying a current density selected to formsparks on said implant, to thereby form a ceramic layer on said implant.

In an embodiment, the ammoniac concentration at 25 vol. % ranges from1.0 mol/L to 6.0 mol/L. In another embodiment, the diammonium hydrogenphosphate concentration ranges from 0.05 mol/L to 0.2 mol/L. In anotherembodiment the urea concentration ranges from 0.01 mol/L to 1.0 mol/L.In an embodiment, the ammoniac concentration at 25 vol. % ranges from1.0 mol/L to 6.0 mol/L and the diammonium hydrogen phosphateconcentration ranges from 0.05 mol/L to 0.2 mol/L. In an embodiment, theammoniac concentration at 25 vol. % ranges from 1.0 mol/L to 6.0 mol/Land the urea concentration ranges from 0.01 mol/L to 1.0 mol/L. In anembodiment, the diammonium hydrogen phosphate concentration ranges from0.05 mol/L to 0.2 mol/L and the urea concentration ranges from 0.01mol/L to 1.0 mol/L.

In some embodiments of the methods, the ammoniac concentration at 25vol. % is selected from the group consisting of 1.0 mol/L, 1.1 mol/L,1.2 mol/L, 1.3 mol/L, 1.4 mol/L, 1.5 mol/L, 1.6 mol/L, 1.7 mol/L, 1.8mol/L, 1.9 mol/L, 2 mol/L, 2.1 mol/L, 2.2 mol/L, 2.3 mol/L, 2.4 mol/L,2.5 mol/L, 2.6 mol/L, 2.7 mol/L, 2.8 mol/L, 2.9 mol/L, 3 mol/L, 3.1mol/L, 3.2 mol/L, 3.3 mol/L, 3.4 mol/L, 3.5 mol/L, 3.6 mol/L, 3.7 mol/L,3.8 mol/L, 3.9 mol/L, 4 mol/L, 4.1 mol/L, 4.2 mol/L, 4.3 mol/L, 4.4mol/L, 4.5 mol/L, 4.6 mol/L, 4.7 mol/L, 4.8 mol/L, 4.9 mol/L, 5 mol/L,5.1 mol/L, 5.2 mol/L, 5.3 mol/L, 5.4 mol/L, 5.5 mol/L, 5.6 mol/L, 5.7mol/L, 5.8 mol/L, 5.9 mol/L, 6 mol/L, and values in between. In someembodiments, the ammoniac concentration at 25 vol. % is at least 1.0mol/L. In some embodiments, the ammoniac concentration at 25 vol. % isgreater than 1.0 mol/L. In some embodiments, the ammoniac concentrationat 25 vol. % is less than 6 mol/L. In some embodiments, the ammoniacconcentration at 25 vol. % is no more than 6 mol/L.

In some embodiments of the methods, the diammonium hydrogen phosphateconcentration is selected from the group consisting 0.05 mol/L, 0.06mol/L, 0.07 mol/L, 0.08 mol/L, 0.09 mol/L, 0.1 mol/L, 0.11 mol/L, 0.12mol/L, 0.13 mol/L, 0.14 mol/L, 0.15 mol/L, 0.16 mol/L, 0.17 mol/L, 0.18mol/L, 0.19 mol/L, 0.2 mol/L, and values in between. In someembodiments, the diammonium hydrogen phosphate concentration is at least0.05 mol/L. In some embodiments, the diammonium hydrogen phosphateconcentration is greater than 0.05 mol/L. In some embodiments, thediammonium hydrogen phosphate concentration is less than 0.2 mol/L. Insome embodiments, the diammonium hydrogen phosphate concentration is nomore than 0.2 mol/L.

In some embodiments of the methods, the urea concentration is selectedfrom the group consisting of 0.01 mol/L, 0.02 mol/L, 0.03 mol/L, 0.04mol/L, 0.05 mol/L, 0.06 mol/L, 0.07 mol/L, 0.08 mol/L, 0.09 mol/L, 0.1mol/L, 0.11 mol/L, 0.12 mol/L, 0.13 mol/L, 0.14 mol/L, 0.15 mol/L, 0.16mol/L, 0.17 mol/L, 0.18 mol/L, 0.19 mol/L, 0.2 mol/L, 0.21 mol/L, 0.22mol/L, 0.23 mol/L, 0.24 mol/L, 0.25 mol/L, 0.26 mol/L, 0.27 mol/L, 0.28mol/L, 0.29 mol/L, 0.3 mol/L, 0.31 mol/L, 0.32 mol/L, 0.33 mol/L, 0.34mol/L, 0.35 mol/L, 0.36 mol/L, 0.37 mol/L, 0.38 mol/L, 0.39 mol/L, 0.4mol/L, 0.41 mol/L, 0.42 mol/L, 0.43 mol/L, 0.44 mol/L, 0.45 mol/L, 0.46mol/L, 0.47 mol/L, 0.48 mol/L, 0.49 mol/L, 0.5 mol/L, 0.51 mol/L, 0.52mol/L, 0.53 mol/L, 0.54 mol/L, 0.55 mol/L, 0.56 mol/L, 0.57 mol/L, 0.58mol/L, 0.59 mol/L, 0.6 mol/L, 0.61 mol/L, 0.62 mol/L, 0.63 mol/L, 0.64mol/L, 0.65 mol/L, 0.66 mol/L, 0.67 mol/L, 0.68 mol/L, 0.69 mol/L, 0.7mol/L, 0.71 mol/L, 0.72 mol/L, 0.73 mol/L, 0.74 mol/L, 0.75 mol/L, 0.76mol/L, 0.77 mol/L, 0.78 mol/L, 0.79 mol/L, 0.8 mol/L, 0.81 mol/L, 0.82mol/L, 0.83 mol/L, 0.84 mol/L, 0.85 mol/L, 0.86 mol/L, 0.87 mol/L, 0.88mol/L, 0.89 mol/L, 0.9 mol/L, 0.91 mol/L, 0.92 mol/L, 0.93 mol/L, 0.94mol/L, 0.95 mol/L, 0.96 mol/L, 0.97 mol/L, 0.98 mol/L, 0.99 mol/L, 1mol/L, and values in between. In some embodiments, the ureaconcentration is at least 0.01 mol/L. In some embodiments, the ureaconcentration is greater than 0.01 mol/L. In some embodiments, the ureaconcentration is less than 1 mol/L. In some embodiments, the ureaconcentration is no more than 1 mol/L.

In an embodiment, the aqueous electrolyte bath has a pH value rangingfrom about 6 to about 14, from about 6 about 13, from about 6 to about12, from about 6 to about 11, from about 6 to about 10, from about 6 toabout 9, from about 6 to about 8, or from about 6 to about 7. In anotherembodiment, the aqueous electrolyte bath has a pH value ranging fromabout 7 to about 14, from about 7 about 13, from about 7 to about 12,from about 7 to about 11, from about 7 to about 10, from about 7 toabout 9, or from about 7 to about 8. In another embodiment, the aqueouselectrolyte bath has a pH value ranging from about 8 to about 14, fromabout 8 about 13, from about 8 to about 12, from about 8 to about 11,from about 8 to about 10, or from about 8 to about 9. In anotherembodiment, the aqueous electrolyte bath has a pH value ranging 9 toabout 14, from about 9 about 13, from about 9 to about 12, from about 9to about 11, or from about 9 to about 10. In another embodiment, theaqueous electrolyte bath has a pH value ranging 10 to about 14, fromabout 10 about 13, from about 10 to about 12, or from about 10 to about11. In another embodiment, the aqueous electrolyte bath has a pH valueranging 11 to about 14, from about 11 about 13, or from about 11 toabout 12. In some embodiments, the aqueous electrolyte bath has a pHvalue of greater than 6. In some embodiments, the aqueous electrolytebath has a pH value of at least 6, at least 7, at least 8, at least 9,at least 10, or at least 11. In some embodiments, the aqueouselectrolyte bath has a pH value of less than 14, less than 13, or lessthan 12. In some embodiments, the aqueous electrolyte bath has a pHvalue of no more than 14. In yet another embodiment, the aqueouselectrolyte bath has a pH value ranging from 10.3 to 11.6.

In an embodiment, the aqueous electrolyte bath has a temperature rangingfrom about 0° C. to about 5° C., from about 10° C. to about 15° C., fromabout 20° C. to about 25° C., from about 30° C. to about 35° C., fromabout 40° C. to about 45° C., from about 45° C. to about 50° C., fromabout 0° C. to about 5° C., from about 0° C. to about 10° C., from about0° C. to about 15° C., from about 0° C. to about 20° C., from about 0°C. to about 25° C., from about 0° C. to about 30° C. to about 35° C.,from about 0° C. to about 40° C., from about 0° C. to about 45° C., fromabout 0° C. to about 45° C., from 0° C. to about 50° C., from about 5°C. to about 10° C., from about 5° C. to about 15° C., from about 5° C.to about 20° C., from about 5° C. to about 25° C., from about 5° C. toabout 30° C., from about 5° C. to about 35° C., from about 5° C. toabout 40° C., from about 5° C. to about 45° C., from 5° C. to about 50°C., from about 10° C. to about 15° C., from about 10° C. to about 20°C., from about 10° C. to about 25° C., from about 10° C. to about 30°C., from about 10° C. to about 35° C., from about 10° C. to about 40°C., from about 10° C. to about 45° C., from 10° C. to about 50° C., fromabout 15° C. to about 20° C., from about 15° C. to about 25° C., fromabout 15° C. to about 30° C., from about 15° C. to about 35° C., fromabout 15° C. to about 40° C., from about 15° C. to about 45° C., from15° C. to about 50° C., from about 20° C. to about 25° C., from about20° C. to about 30° C., from about 20° C. to about 35° C., from about20° C. to about 40° C., from about 20° C. to about 45° C., from 20° C.to about 50° C., from about 25° C. to about 30° C., from about 25° C. toabout 35° C., from about 25° C. to about 40° C., from about 25° C. toabout 45° C., from 25° C. to about 50° C., from about 30° C. to about35° C., from about 30° C. to about 40° C., from about 30° C. to about45° C., from 30° C. to about 50° C., from about 35° C. to about 40° C.,from about 35° C. to about 45° C., from about 35° C. to about 45° C.,from 35° C. to about 50° C., from about 40° C. to about 45° C., from 40°C. to about 50° C., or from 45° C. to about 50° C. In anotherembodiment, the aqueous electrolyte bath has a temperature ranging from18° C. to 22° C.

In an embodiment, the current density ranges from 1 A/dm² to 1.2 A/dm²,from 1 A/dm² to 1.3 A/dm², from 1 A/dm² to 1.4 A/dm², from 1 A/dm² to1.5 A/dm², from 1 A/dm² to 1.6 A/dm², from 1 A/dm² to 1.7 A/dm², from 1A/dm² to 1.8 A/dm², from 1 A/dm² to 1.9 A/dm², from 1 A/dm² to 2 A/dm²,from 1 A/dm² to 2.1 A/dm², from 1 A/dm² to 2.2 A/dm², from 1 A/dm² to2.3 A/dm², from 1 A/dm² to 2.4 A/dm², from 1 A/dm² to 2.5 A/dm², from 1A/dm² to 2.6 A/dm², from 1 A/dm² to 2.7 A/dm², from 1 A/dm² to 2.8A/dm², from 1 A/dm² to 2.9 A/dm², or from 1 A/dm² to 3 A/dm². In anotherembodiment, the current density is at least 1 A/dm². In someembodiments, the current density is greater than 1 A/dm². In someembodiments, the current density is less than 3 A/dm². In someembodiments, the current density is no more than 3 A/dm².

In an embodiment, a method of the present invention provides for forminga ceramic coating on selected portions of the surface area of theimplant. In an embodiment, selected portions of the surface area of theimplant are electrically insulated to allow selective anodization of theregions of the surface of the implant that are not electricallyinsulated. In an embodiment, the electric insulation of the areas whichare not to be coated is achieved by applying a lacquer, film or foil orthe like to the desired regions of the surface area of the implant, andsubsequent to the coating process, the applied lacquer, film or foil isremoved (by manual delamination, for example).

It will be understood by those of ordinary skill in the art that a widevariety of coating patterns may be designed and applied to implants.Those of ordinary skill in the art that would also know that theposition and dimensions of the selectively coated regions of the surfacearea of the implant may be varied to modulate the corrosion performancethe coated implant. For example, the selectively coated regions of theimplant would be expected to degrade at a slower rate than the uncoatedregions because the coat the reactants must first penetrate the coat orerode it before reaching the coated surface of the reactive surface ofthe implant.

In an embodiment of the magnesium implant with a ceramic layer, saidceramic layer comprises an oxide, hydroxide, phosphate or combinationsthereof. In an embodiment of the magnesium implant with a ceramic layer,said ceramic layer comprises an oxide. In an embodiment of the magnesiumimplant with a ceramic layer, said ceramic layer comprises a hydroxide.In an embodiment of the magnesium implant with a ceramic layer, saidceramic layer comprises phosphate. In an embodiment of the magnesiumimplant with a ceramic layer, said ceramic layer comprises an oxide anda hydroxide. In an embodiment of the magnesium implant with a ceramiclayer, said ceramic layer comprises an oxide and a phosphate. In anembodiment of the magnesium implant with a ceramic layer, said ceramiclayer comprises a hydroxide and a phosphate. In another embodiment ofthe magnesium implant with a ceramic layer, said ceramic layer comprisesan oxide, a hydroxide and a phosphate. In another embodiment of themagnesium implant with a ceramic layer, said ceramic layer is selectedfrom the group consisting of: MgO, Mg(OH)₂, Mg₃(PO₄)₂ and oxides ofalloying elements of magnesium.

In an embodiment of the magnesium implant with a ceramic layer, saidceramic layer has a thickness of up to 50 μm. In an embodiment of themagnesium implant with a ceramic layer, said ceramic layer has athickness ranging from about 1 μm to about 5 μm, from about 10 μm toabout 15 μm, from about 20 μm to about 25 μm, from about 30 μm to about35 μm, from about 40 μm to about 45 μm, from about 45 μm to about 50 μm,from about 1 μm to about 5 μm, from about 1 μm to about 10 μm, fromabout 1 μm to about 15 μm, from about 1 μm to about 20 μm, from about 1μm to about 25 μm, from about 1 μm to about 30 μm to about 35 μm, fromabout 1 μm to about 40 μm, from about 1 μm to about 45 μm, from about 1μm to about 45 μm, from 1 μm to about 50 μm, from about 5 μm to about 10μm, from about 5 μm to about 15 μm, from about 5 μm to about 20 μm, fromabout 5 μm to about 25 μm, from about 5 μm to about 30 μm, from about 5μm to about 35 μm, from about 5 μm to about 40 μm, from about 5 μm toabout 45 μm, from 5 μm to about 50 μm, from about 10 μm to about 15 μm,from about 10 μm to about 20 μm, from about 10 μm to about 25 μm, fromabout 10 μm to about 30 μm, from about 10 μm to about 35 μm, from about10 μm to about 40 μm, from about 10 μm to about 45 μm, from 10 μm toabout 50 μm, from about 15 μm to about 20 μm, from about 15 μm to about25 μm, from about 15 μm to about 30 μm, from about 15 μm to about 35 μm,from about 15 μm to about 40 μm, from about 15 μm to about 45 μm, from15 μm to about 50 μm, from about 20 μm to about 25 μm, from about 20 μmto about 30 μm, from about 20 μm to about 35 μm, from about 20 μm toabout 40 μm, from about 20 μm to about 45 μm, from 20 μm to about 50 μm,from about 25 μm to about 30 μm, from about 25 μm to about 35 μm, fromabout 25 μm to about 40 μm, from about 25 μm to about 45 μm, from 25 μmto about 50 μm, from about 30 μm to about 35 μm, from about 30 μm toabout 40 μm, from about 30 μm to about 45 μm, from 30 μm to about 50 μm,from about 35 μm to about 40 μm, from about 35 μm to about 45 μm, fromabout 35 μm to about 45 μm, from 35 μm to about 50 μm, from about 40 μmto about 45 μm, from 40 μm to about 50 μm, or from 45 μm to about 50 μm.In another embodiment, the magnesium implant with a ceramic layer, saidceramic layer has a thickness ranging from 2 μm to 20 μm. In someembodiments, the ceramic layer is at least or greater than 1 μm inthickness, at least or greater than 2 μm in thickness, at least orgreater than 5 μm in thickness, at least or greater than 10 μm inthickness, at least or greater than 15 μm in thickness, at least orgreater than 20 μm in thickness, at least or greater than 25 μm inthickness, at least or greater than 30 μm in thickness, at least orgreater than 35 μm in thickness, at least or greater than 40 μm inthickness, at least or greater than 45 μm in thickness, or at least orgreater than 50 μm in thickness. In some embodiments, the ceramic layeris no more than 50 μm in thickness.

The magnesium implant with a ceramic layer made by the methods of thepresent invention advantageously has a ceramic layer that not onlyimproves bone tissue adhesion, but also is substantially free ofsubstances which impair the biocompatibility. In an embodiment, thebiocompatible ceramic layer is substantially free of material whichimpairs the biocompatibility of said biocompatible ceramic layer. In anembodiment, said biocompatible ceramic layer typically will have athickness of up to 50 μm. In one such embodiment, said material whichimpairs the biocompatibility of said biocompatible ceramic layercomprises an amine decomposition product. In another embodiment,biocompatible ceramic layer includes a component selected from the groupconsisting of MgO, Mg(OH)₂, Mg₃(PO₄)₂, oxides of alloying elements ofmagnesium and combinations thereof. Another advantage of the magnesiumimplant with a ceramic layer made by the methods of the presentinvention is that said implant delays and/or reduces hydrogen release,compared to a magnesium implant without said biocompatible ceramiclayer, when immersed in a simulated body fluid, for example.

Accordingly, in an embodiment of the magnesium implant with a ceramiclayer according to the present invention, said ceramic layer reduceshydrogen release with respect to the corroded mass of magnesium comparedto a magnesium implant without said ceramic layer by 10% to 50% over animmersion period of up to 40 days. In an embodiment, said ceramic coatedmagnesium implant reduces hydrogen release with respect to the corrodedmass of magnesium compared to a magnesium implant without said ceramiclayer by from about 10% to about 15%, from about 10% to about 20%, fromabout 10% to about 25%, from about 10% to about 30%, from about 10% toabout 35%, from about 10% to about 40%, from about 10% to about 45%,from 10% to about 50%, from about 15% to about 20%, from about 15% toabout 25%, from about 15% to about 30%, from about 15% to about 35%,from about 15% to about 40%, from about 15% to about 45%, from 15% toabout 50%, from about 20% to about 25%, from about 20% to about 30%,from about 20% to about 35%, from about 20% to about 40%, from about 20%to about 45%, from 20% to about 50%, from about 25% to about 30%, fromabout 25% to about 35%, from about 25% to about 40%, from about 25% toabout 45%, from 25% to about 50%, from about 30% to about 35%, fromabout 30% to about 40%, from about 30% to about 45%, from 30% to about50%, from about 35% to about 40%, from about 35% to about 45%, fromabout 35% to about 45%, from 35% to about 50%, from about 40% to about45%, from 40% to about 50%, or from 45% to about 50% over an immersionperiod of from 5 days to 10 days, from 5 days to 15 days, from 5 days to20 days, from 5 days to 25 days, from 5 days to 30 days, from 5 days to35 days, from 5 days to 40 days, from 10 days to 15 days, from 10 daysto 20 days, from 10 days to 25 days, from 10 days to 30 days, from 10days to 35 days, from 10 days to 40 days, from 15 days to 20 days, from15 days to 25 days, from 15 days to 30 days, from 15 days to 35 days,from 15 days to 40 days, from 20 days to 25 days, from 20 days to 30days, from 20 days to 35 days, from 20 days to 40 days, from 25 days to30 days, from 25 days to 35 days, from 25 days to 40 days, from 30 daysto 35 days, from 30 days to 40 days, or from 35 days to 40 days.

The materials and implants according to embodiments of the presentinvention may be configured for use as any medical implants known in theart constructed from magnesium or its alloys. In some embodiments,implants of the present invention are useful as bone implants, fixationdevices, and/or for osteosynthesis. In some embodiments, the implants ofthe present invention are configured to be biodegradable. In someembodiments, the present invention includes a bone plate made from thematerials disclosed herein. In some embodiments, the bone plate of thepresent invention is constructed from magnesium or its alloys. In someembodiments, the bone plate is entirely or at least partially coatedwith a coating or ceramic layer as described herein. In someembodiments, the bone plate is only partially coated. Bone platesaccording to some embodiments of the present invention are configuredfor attachment to one or more bones or bone fragments and may have anygeneral shape known in the art suitable for bone fixation,osteosynthesis, compression and/or bone fusion. In some embodiments, thebone plates include one or more fixation holes for receiving a bonescrew, tack, nail, or other fixation device for attachment to bone. Insome embodiments, the bone plates may have a substantially linear orlongitudinal configuration. In some embodiments, for example, the boneplate may have a plurality of fixation holes that are arrangedsubstantially linearly or in a single row. In other embodiments, thebone plate may include a plurality of fixation holes that are arrangedin a plurality of rows, for example, in a two dimensional array.

FIGS. 16A-16D illustrate example bone plates 100, 110, 120, and 130according to embodiments of the invention, showing different possibleconfigurations. Bone plates 100, 110, 120, and 130 may include one ormore holes for receiving fixation devices, for example, bone screws 102,112, 122, and 132. In some embodiments, bone plates 100, 110, 120, and130 are made from magnesium or a biocompatible magnesium alloy and maybe entirely or at least partially coated with a ceramic coating or layeras described herein. In some embodiments, bone plates 100, 110, 120, and130 are only partially coated. In some embodiments, bone screws 102,112, 122, and 132 are made from the same materials as bone plates 100,110, 120, and 130, respectively. In some embodiments, bone screws 102,112, 122, and 132 are made from magnesium or a biocompatible magnesiumalloy and may be entirely or at least partially coated with a ceramiccoating or layer as described herein. In some embodiments, the portionsof bone plates 100, 110, 120, and 130 and/or bone screws 102, 112, 122,and 132 to be coated are coated by exposure to an aqueous electrolytebath containing, consisting of, or consisting essentially of ammoniac,diammonium hydrogen phosphate, and urea as described herein.

FIGS. 17A and 17B illustrate further example bone plates 140 and 150according to embodiments of the invention. In some embodiments, boneplates 140 and 150 respectively include holes 142 and 152 for receivingfixation devices (not shown), such as a bone screw, nail, or tack. Insome embodiments, bone plates 140 and 150 may further includecountersinking 144 and 154 around holes 142 and 152. In someembodiments, bone plates 140 and 150 may be constructed from magnesiumor a biocompatible magnesium alloy. In some embodiments, bone plates 140and 150 are entirely or at least partially coated with a ceramic coatingor layer as described herein. In some embodiments, bone plates 140 and150 are only partially coated. For example, in some embodiments, theinternal surfaces of holes 142 and 152 remain uncoated. In someembodiments, countersinking 144 and 154 remain uncoated. In someembodiments, the portions of bone plates 140 and 150 to be coated arecoated by exposure to an aqueous electrolyte bath containing, consistingof, or consisting essentially of ammoniac, diammonium hydrogenphosphate, and urea as described herein.

Other example bone plate configurations that may be used according tosome embodiments of the present invention may be found in U.S. PatentApplication Publication Nos. US 2003/0004515 A1 and US 2008/0009872 A1,which are each incorporated herein by reference in its entirety.

These and other aspects of the present invention will be furtherappreciated upon consideration of the following Examples, which areintended to illustrate certain particular embodiments of the inventionbut are not intended to limit its scope, as defined by the claims.

EXAMPLE 1 Lean Electrolyte Compositions

Coatings were made on rectangular magnesium plates with 10 cm² surfacearea immersed in selected electrolyte compositions, using a directcurrent of 0.16 A, a maximum tension of 400 V and a coating time of 10minutes. The electrolyte compositions used are as follows:

Composition of electrolyte A: 0.13 mol/L diammonium hydrogen phosphate,1.07 mol/L ammoniac (25%), and 0.50 mol/L urea.

Composition of electrolyte B: 0.05 mol/L diammonium hydrogen phosphate,5.36 mol/L ammoniac (25%), and 0.50 mol/L urea.

FIG. 1 shows an SEM image of a coating on a magnesium plate with coarsepores produced using electrolyte A, after plastic deformation. FIG. 2shows an SEM image of a coating on a magnesium plate with fine poresproduced using electrolyte B, after plastic deformation. The compositionof the electrolyte was the major parameter for the pore size as allother parameters were identical between the two samples.

The size and distribution of the pores may be important for the failurebehavior of the implant. After plastic deformation and elastictensioning, the sample with the coarse pores (FIG. 1) shows broadercracks than the sample with fine pores (FIG. 2) where the cracks arefiner and more evenly distributed. It is presumed that corrosion attackmay be more localized with the coarser pores, which might also act asstress risers.

EXAMPLE 2 In Vivo Degradation

Experiment:

All animal experiments were conducted in accordance with the Swissanimal protection law. Fourteen skeletally mature miniature pigs eachwith an age of 30 to 36 months and an average weight of 53±7 kg wereused in this preliminary study.

The midface of the miniature pig is approached by a T-type incisionwhere as a median cut of 11-12 cm length was started about 2 cm belowthe lower orbits. After exposing the frontal bone, a soft tissue pocketwas created with a rasp, big enough to accommodate the two rectangularplates and deep enough to profit of the straight portion of the nasalbone. Pre-bending of the plates could therefore be avoided. FIG. 3illustrates the positioning of implanted plates 10 a and 10 b on a pigskull 12 in accordance with this Example. Each miniature pig receivedeither two coated or two non-coated magnesium plates. The coated plateswere coated in accordance with Example 3 below.

In addition to the post-operative X-rays of the head, intermediateradiographs (Philips BVPulsera) were taken at 1, 4, 8, and 12 weeks.FIG. 7 shows an X-ray image of a non-coated magnesium plate implanted ina miniature pig after 1 week. FIG. 8 shows an X-ray image of a coatedmagnesium plate implanted in a miniature pig at 12 weeks beforeeuthanasia. The animals were sacrificed after 12 and 24 weeks. Aftereuthanasia, a computed X-ray tomography (CT) was made. A medial incisionof about 10 cm length was made along the longitudinal axis of the noseand the implants were removed. The pH of the implant bed was determinedusing pH sensitive strip (Merck 1.09557.0003, pH range 6.4-8.0) whichwas moistened with distilled water before use. The removed plates werestored in 70% ethanol in a tightly sealed glass bottle. Aftertransportation to the mechanical testing site, the magnesium plates wereremoved from the glass bottles, dabbed with paper towel and dried inair.

Energy dispersive X-ray spectroscopy (EDX) measurements were carried outin a Zeiss EVO60 scanning electron microscope (SEM) using a THERMOScientific ultra dry EDX detector. The measured spectra were analyzedfor the elements C, O, Mg, P, Ca, Y, Zr, Nd, Gd, Dy, Er, Yb, Na and K.Chlorine (Cl) was excluded from the analysis as it could not be detectedon any of the spectra. Three areas of about 100 μm×100 μm were measuredon each sample to determine the EDX-spectra. The weight loss wasdetermined after brushing off the degradation products with a nailbrush. Additionally, the plates were immersed in 40% hydrofluoric acidfor at least 5 minutes as described by A. Krause et al. (“Degradationbehavior and mechanical properties of magnesium implants in rabbittibiae” Journal of Materials Science 2010, 45, 624-632, incorporatedherein by reference in its entirety), cleaned in distilled water andethanol and dried with an air blower.

Results:

The occurrence of gas bubbles might be taken as an indicator for the invivo degradation. As the exposed surface of the magnesium plates is verylarge (2×9 cm²), a daily release of about 5 ml might be expected whenusing the in vitro gas release rate of 0.3 ml/cm² per day. If thisamount of gas could not be transported away, gas bubbles would form inthe thick soft tissue on top of the plates. Intermediate X-rays wereused to check the occurrence of gas bubbles and the integrity of therectangular plates. For the non-coated plates, gas bubbles could beobserved in most of the animals after 1 week. The large observed gasbubble in the case of one animal disappeared by week 4. For the coatedplates, the occurrence of gas bubbles was delayed. First signs of gaspockets often occurred around the thread holes and started to appear byweek 4. No signs of loose tissue could be seen around the titaniumcontrol plates. The additional CT images show the situation aftereuthanasia and before the removal of the plates. The plates did not seemto be much corroded upon removal. The plates removed at 24 weeks showedlarger areas with white corrosion products than the plates at 12 weeks.The two sides of the plates were not equally corroded; the top side incontact with the soft tissue seemed more corroded than the bottom sidein contact with the frontal bone. The plates seemed well integrated tothe surrounding tissue as a lateral step seemed to have formed in thebone. On one animal of each 24 week group, the pH of the implant bedswas determined after removal of the plate. No difference in pH could befound for the coated and non-coated groups compared to the titaniumreference. pH values of 7.0-7.2 were typically found. The white,enamel-like degradation products seemed more compact and more adherentcompared to the in vitro situation. As a consequence, the brushing offof the degradation products was not sufficient and additional bathing inhydrofluoric acid was used to determine the total weight loss. For bothkind of plates, the average weight loss was about 5-6% after 12 weeksand increased to 13-14% after 24 weeks. The results of the EDX analysisof the in vivo degradation products prior to the brush off showedsignificantly higher calcium and phosphor contents for the coatedmagnesium plates for each milligram of corroded metal and are summarizedin Table I below.

TABLE I EDX analysis of degraded implant surface before brushing offdegradation products. Chemical Non-coated Non-coated Coated Coatedelements [wt %] 12 weeks 24 weeks 12 weeks 24 weeks Carbon 11 ± 6 16 ±14  26 ± 11 18 ± 8 Oxygen 42 ± 5 42 ± 9  31 ± 5 33 ± 3 Magnesium 13 ± 213 ± 5   3.3 ± 1.3  4.2 ± 1.4 Calcium  2.5 ± 0.7 2.6 ± 2.2 14 ± 6 12 ± 7Phosphor  3.8 ± 1.4 4.4 ± 4.1 12 ± 3 10 ± 4 Yttrium, Zirconium 28 ± 2 22± 2  13 ± 7  23 ± 16 & rare earths

EXAMPLE 3 Alloy and Coating

Based on the composition of the magnesium alloy WE43 (chemicalcomposition: Mg—Y—Nd heavy rare earths), a new alloy was developed.Implants from the same lot were used for all experiments (lot MI0018B,T5 heat treated, 6.4×19 mm extrusion profile). The rectangular plateswith 60 mm×6.0 mm×1.50 mm were machined dry (w/o lubricant) using hardmetal tools. All edges were rounded with a radius of 0.5 mm. A total of36 plates were tested, half of the plates without a coating and theother half with a plasmaelectrolytic coating from AHC (Kerpen, Germany).A standard MAGOXID™ electrolyte was used and a direct current of 1.4A/dm² for up to 400 V was applied to generate the coating. Non-coatedplates initially weighted 940±5 mg. The MAGOXID™ coating had a typicalthickness of 10 μm and accounted for 15 mg of additional mass. The totalsurface of a plate was 9 cm². The plates were cleaned with ultrasoundassistance in 90-100% ethanol, dried in air, packaged in pairs of two ina double vacuum pouch and γ-sterilized with a dose of 25-30 kGy.

EXAMPLE 4 In Vitro Immersion Testing

Experiment:

Coated and non-coated samples were each tested inside a separateimmersion unit containing 250 ml of simulated body fluid (SBF). Coatedsamples were prepared in accordance with Example 3 above. An immersionunit consisted of a graduated glass cylinder with 25 mm inner diameterand 240 mm length and a 250 ml plastic bottle. Each magnesium sample wasput inside the glass cylinder which was then filled with SBF. Theplastic bottle was put upside down over the glass cylinder. Thecylinder/bottle assembly was quickly tilted to avoid the flowing out ofthe liquid and the remaining SBF was poured into the gap between bottleand glass cylinder. Finally, the lid of the bottle—which had a 33 mmhole—was slid over the glass cylinder to fix the assembly. The bottleswere put inside a tempered water bath at 37° C.

The simulated body fluid was prepared from stock solutions as describedby L. Müller and F. A. Müller [“Preparation of SBF with different HCO₃—content and its influence on the composition of biomimetic apatites”Acta Biomaterialia 2 (2006) 181-9, incorporated herein by reference inits entirety] with TRIS buffer and the recipe for a HCO₃— content of 27mmol/L. The addition of NaN₃ was omitted as no bacterial growth wasobserved and as N₂ release into the medium could be avoided. The mediumwas changed once a week. Identical material lots, coatings andgeometries were used for the in vitro and the in vivo degradation tests.The samples were immersed for 4, 8 and 12 weeks. The gas release wasdetermined by regular visual inspection of the graded glass cylinderswith a precision of about ±1 ml. The average mass loss was determined atthe end of the immersion period by brushing off the corrosion productswith a common nail brush.

Results:

The average gas release during immersion in SBF can be seen in FIG. 5,which shows a graph depicting the average gas release rate of coated andnon-coated rectangular plates immersed in SBF for up to 12 weeks(average of 6 tests per data point). The non-coated samples started torelease gas directly after immersion. Initial gas release rates werehighest during the first couple of days (>1 ml/cm² per day) and thenstabilized around 0.3 ml/cm² per day. On the other hand, the coatedsamples showed nearly no gas release during the first two weeks. The gasrelease rates then started to increase and stabilized around 0.2 ml/cm²per day. The degradation of non-coated magnesium samples was uniformover the entire immersion time. Some localized corrosion seemed to occurfor the coated magnesium samples at 12 weeks which might be associatedwith a slight increase in the gas release rate around day 65 (9-10weeks). The mass loss of the samples—determined by brushing off thepowder-like white corrosion products—could be put into relation with theobserved gas release as shown in FIG. 6, which is a graph depicting gasrelease as a function of weight loss of coated and non-coated platesimmersed in SBF for up to 12 weeks (average of 6 tests per data point).For the non-coated samples, about 1 ml of gas is released for 1 mg ofcorroded magnesium as theoretically expected from the overall corrosionreaction. For the coated magnesium, however, less gas was released thanexpected; only around 0.6 ml of gas could be collected

EXAMPLE 5 Mechanical Testing

Experiment:

The 3-point-bending tests of the in vivo and in vitro degraded samplesfrom Examples 2 and 4 were made using a small Zwick/Roell universaltesting machine (type BZ2.5/TN1S) with a test device according to ISO EN178. FIG. 4 illustrates a depiction of the 3-point-bending test showinga sample 20 positioned on two support brackets 22 a and 22 b being bentby a downward moving plunger 24. A span of 40 mm was used for all theplates. The support brackets had a radius of 2 mm. The plunger was 4 mmin diameter and was moved downwards at a rate of 1 mm/min. The test wasstopped after 10 mm of displacement. Forces were recorded with aprecision of ±0.5% (2 kN force gauge).

Results:

The measured maximum bending force, bending stress, yield strength andflexural modulus are given in Table II for the non-coated and in TableIII for the coated implants below. Each value averages 6 samples, fromindividual bottles for the in vitro case and from 3 different animals inthe in vivo case (pairs of two). FIG. 9 is a graph further showing thedecrease of yield strength over time for in vitro and in vivo degradedcoated and non-coated rectangular plates.

TABLE II Strength retention of non-coated rectangular magnesium platesafter in vitro and in vivo degradation. Mechanical Maximum MaximumFlexural Yield property bending flexural modulus strength Time pointforce [N] strength [MPa] [GPa] [MPa] Titanium 213 972 100 805 Nondegraded 91.6 ± 1.2 402 ± 5  41.5 ± 0.5 336 ± 2  In vitro 82.9 ± 3.1 361± 16 32.0 ± 2.0 285 ± 12 4 weeks In vitro 61.3 ± 9.0 279 ± 38 24.4 ± 3.7224 ± 30 8 weeks In vitro 48.9 ± 8.7 241 ± 30 18.7 ± 3.8 192 ± 24 12weeks In vivo 86.7 ± 4.6 367 ± 20 29.5 ± 2.4 270 ± 13 12 weeks In vivo80.0 ± 6.4 346 ± 33 28.0 ± 4.8 264 ± 26 24 weeks

TABLE III Strength retention of coated rectangular magnesium platesafter in vitro and in vivo degradation. Mechanical Maximum MaximumFlexural Yield property bending flexural modulus strength Time pointforce [N] strength [MPa] [GPa] [MPa] Non degraded 91.5 ± 2.0 393 ± 7 39.2 ± 0.6 316 ± 4  In vitro 102.4 ± 5.6  437 ± 24 35.5 ± 0.8 308 ± 3  4weeks In vitro 73.6 ± 3.5 332 ± 15 28.6 ± 1.9 252 ± 12 8 weeks In vitro 60.2 ± 20.8 280 ± 92 24.7 ± 3.6 213 ± 57 12 weeks In vivo 92.7 ± 3.9394 ± 16 33.3 ± 1.8 290 ± 12 12 weeks In vivo 83.9 ± 3.9 363 ± 21 27.9 ±3.9 268 ± 12 24 weeks

All in vivo degraded plates could be deformed to the final bendingposition without breaking. In addition to those 3-point-bending tests onin vivo and in vitro degraded plates, the chosen 3-point-bending setupwith a constant span of 40 mm was verified with a series of rectangularplates to check if the changed dimensions of the degraded plates wouldgive correct strength measurements. A uniform degradation was“simulated” by decreasing the thickness and width of the plates in 0.2mm steps down to a thickness of 0.5 mm and to a width of 5.0 mm.According to theory, the bending force F is expected to depend on thethickness d and on the width b as follows:

$F = {\frac{2}{3}\frac{\sigma_{b}}{L}{bd}^{2}}$with the span L and the bending stress σ_(b) When assuming a constantbending stress, σ_(b)=MPa, an excellent fit between the measured maximumforces (results not shown) and the theoretical values was obtained (ΔF≦2N). This relation might be used to calculate the core thickness of adegraded plate and to assess the uniformity of degradation.

EXAMPLE 6 Anodic Oxidation

Experiment:

The magnesium implant of WE43 alloy used in this experiment had asurface of 0.1 dm². It was degreased, pickled and rinsed with asepticwater. The WE43 alloy was treated with an aqueous electrolyte bathconsisting of:

-   -   1.07 mol/L ammoniac (25%) (80 ml/L);    -   0.13 mol/L diammonium hydrogen phosphate; and    -   0.5 mol/L urea.

The magnesium implant was hung into the aqueous electrolyte bath and thepositive pole was connected to a D.C. current source. A sheet ofstainless steel was also put inside the aqueous electrolyte bath and wasconnected to the negative pole of the D.C. current source. The currentdensity was set to 1.4 A/dm². The “ceramization” of the magnesiumimplant was carried out for 8 minutes. The final voltage was set to 360V.

Results:

The obtained ceramic layer had a thickness of 11 μm. The “ceramized”magnesium implant was taken out of the electrolyte bath and was rinsedwell with aseptic, de-ionised water and subsequently dried. Chemicalanalysis of the produced ceramic layer on the WE43-magnesium implantshowed MgO, Mg(OH)₂ and small amounts of Mg₃(PO₄)₂, Yttrium oxide andoxides of rare earth elements.

Other magnesium wrought alloys such as WE54, ZK40, ZK, 60, AZ31 as wellas magnesium cast alloys such as AZ91, AM50, AS41 can similarly beceramized (with stainless steel and platinum as cathode materials, forexample) with the procedure of Example 6.

EXAMPLE 7 In Vitro Degradation Behavior of WE43 Samples

Experiment:

In vitro degradation behavior of non-coated and coated WE43 magnesiumalloy samples during immersion in simulated body fluid (SBF) is shownFIG. 10. Magnesium WE43 samples with coatings from three differentelectrolytes exhibit a significantly reduced hydrogen release comparedto non-coated WE43 alloy samples. The three electrolytes contained thefollowing:

-   -   Electrolyte 1: diammonium hydrogen phosphate and ammoniac.    -   Electrolyte 2: diammonium hydrogen phosphate, ammoniac, and        urea.    -   Electrolyte 3: citric acid, boric acid, phosphoric acid, and        ammoniac.

EXAMPLE 8 Gas Release and Strength Retention of Tensioned WE43 SamplesImmersed in SBF

Experiment:

Rectangular samples of WE43 alloy (60 mm×8.0 mm×0.50 mm) were drymachined (w/o lubricant) using hard metal tools. A portion of thesamples were coated with a plasmaelectrolytic coating from AHC (Kerpen,Germany). The electrolyte compositions used for the plasmaelectrolyticcoating are variations of the standard MAGOXID™ electrolyte. A directcurrent of 1.4 A/dm² for up to 400 V was applied to generate thecoating. Other sample lots were coated using different lean electrolytescomprising varying percentages of diammonium hydrogen phosphate,ammoniac (at 25 vol. % concentration), and urea, the ratios of which areshown in Table IV below.

The rectangular samples were manually deformed by bending the endsaround a cylinder with a 16 mm diameter. The amount of bending isdefined by the span of the two ends of the rectangular sample in arelaxed state. A span of about 42 mm was applied to the samples as shownin FIG. 14A, which depicts an example of a manually deformed sample 30.The bent samples were then put under tension by inserting each of theends of a sample into slots spaced about 12 mm apart in a UHMWPE sampleholder. FIG. 14B shows example sample 30 after the ends of which havebeen inserted into slots 34 a and 34 b of sample holder 32 undertension.

Immersion tests of the tensioned were performed by placing tensionedsamples inside separate immersion units containing 250 ml of SBF in amanner similar to the process described in Example 4 for a total of sixweeks. The 250 ml of SBF was exchanged once a week. Gas levels wererecorded twice on working days and occurrence of failure was visuallychecked for the samples.

Strength retention tests were also carried out on immersed samples usingsample holders with screw fixation (FIG. 15A-15D). During the weekly SBFchanges, the screw of the holder is loosened and the spring force abovethe holder is measured by a push pin (indicated by the arrow in FIG.15A). The samples did not need to be removed from the holder during theprocedure. The samples were left in the SBF for 6 weeks irrespective ofeventual failure (breakage) of the sample (e.g., shown in FIGS. 15C and15D).

Results:

All the tested coatings had an excellent adherence to the base materialand did not delaminate during the large plastic deformation applied tothe samples. Plastic deformation did introduce microcracks into thecoating which broadened during the additional tensioning and allowedgreater access to the corrosive SBF medium. Despite the severe testingconditions, the gas release rates of the lean electrolyte-coated sampleswere found to be between about 0.2 ml/cm² per day and about 0.4 ml/cm²per day, and were generally below the values for the non-coated basematerial which ranged from about 0.4 ml/cm² per day to about 0.6 ml/cm²per day. The average accumulated gas release of the leanelectrolyte-coated rectangular samples under tension and immersed in SBFover time is shown in the graph of FIG. 11. The strength retentionmeasurements of the lean electrolyte-coated samples is shown in FIG. 12,which is a graph depicting remaining bending force as a function ofimmersion time.

The failure times of tensioned rectangles during immersion in SBF areshown in the box plot of FIG. 13, which illustrates differences betweenthe various coatings. Four of the five non-coated samples failed after32 days of immersion. The specimens coated with the lean electrolytesshowed a larger degree of variance with some samples withstanding the 42days of immersion without failing while others failed prior to thenon-coated samples. The strength retention (remaining bending force)testing, which was applied only to the coated samples, may haveaccelerated the failure of the coated samples compared to the non-coatedsamples. Moreover, variations in the manual force applied to bend andtension the samples may have contributed to the wider scatter ofresults. Additional time to failure and gas release rate data for thelean electrolyte-coated samples are provided in Table IV below.

TABLE IV diammonium gas average hydrogen time to release hydrogen timeto electrolyte phosphate ammoniac urea failure linear release ratefailure block [%] [%] [%] [days] regression [mg/cm²day] [days] 4.1 48.1514.81 37.04 16.9 1.67 0.22 21.6 48.15 14.81 37.04 5.8 2.65 48.15 14.8137.04 42.0 2.13 5.1 38.61 35.91 25.48 6.7 2.29 0.23 10.7 38.61 35.9125.48 19.7 2.20 38.61 35.91 25.48 5.8 2.26 6.1 20.00 80.00 0.00 29.23.36 0.29 37.1 20.00 80.00 0.00 42.00 2.43 20.00 80.00 0.00 40.00 2.897.1 83.33 16.67 0.00 42.0 2.06 0.22 32.2 83.33 16.67 0.00 12.7 2.1983.33 16.67 0.00 42.0 2.26 8.1 17.24 13.79 68.97 42.0 1.06 0.23 41.317.24 13.79 68.97 42.0 2.54 17.24 13.79 68.97 40.0 3.26 9.1 18.52 44.4437.04 42.0 2.50 0.29 30.3 18.52 44.44 37.04 42.0 3.48 18.52 44.44 37.047.0 2.66 10.1 52.00 48.00 0.00 2.0 1.19 0.18 19.9 52.00 48.00 0.00 15.82.52 52.00 48.00 0.00 42.0 1.64 4.2 48.15 14.81 37.04 42.0 2.44 0.2642.0 48.15 14.81 37.04 42.0 2.87 48.15 14.81 37.04 42.0 2.36 10.2 52.0048.00 0.00 42.0 2.41 0.28 39.6 52.00 48.00 0.00 34.7 3.00 52.00 48.000.00 42.0 2.99 8.2 17.24 13.79 68.97 24.7 3.35 0.32 31.1 17.24 13.7968.97 26.7 3.74 17.24 13.79 68.97 42.0 2.57 5.2 38.61 35.91 25.48 42.02.80 0.28 42.0 38.61 35.91 25.48 42.0 2.71 38.61 35.91 25.48 42.0 2.799.2 18.52 44.44 37.04 37.0 4.15 0.36 39.7 18.52 44.44 37.04 41.0 3.1818.52 44.44 37.04 41.0 3.53 6.1 20.00 80.00 0.00 42.0 3.46 0.33 38.920.00 80.00 0.00 34.1 3.48 20.00 80.00 0.00 40.7 2.81 7.2 83.33 16.670.00 42.0 2.55 0.26 37.3 83.33 16.67 0.00 27.8 2.93 83.33 16.67 0.0042.0 2.28

It should be understood that various changes, substitutions, andalterations can be made herein without departing from the spirit andscope of the invention as defined by the appended claims. It should alsobe apparent that individual elements identified herein as belonging to aparticular embodiment may be included in other embodiments of theinvention. Moreover, the scope of the present application is notintended to be limited to the particular embodiments of the process,machine, manufacture, and composition of matter, means, methods andsteps described in the specification. As one of ordinary skill in theart will readily appreciate from the disclosure herein, processes,machines, manufacture, composition of matter, means, methods, or steps,presently existing or later to be developed that perform substantiallythe same function or achieve substantially the same result as thecorresponding embodiments described herein may be utilized according tothe present invention.

The invention claimed is:
 1. A method of producing ceramic layers onmagnesium and its alloys, comprising the steps of: immersing an implantand a metal sheet into an aqueous electrolyte bath, said aqueouselectrolyte bath consisting essentially of: ammoniac, diammoniumhydrogen phosphate and urea, and wherein the implant is made ofmagnesium or its alloy; performing an anodic oxidation by passing acurrent between the implant, the metal sheet and through the aqueouselectrolyte bath, wherein the implant is connected to a positive pole ofa current source and the metal sheet is connected to a negative pole ofthe current source; applying a current density selected to form sparkson said implant, to thereby form a ceramic layer on said implant.
 2. Themethod according to claim 1, wherein the ammoniac concentration at 25vol. % ranges from 1.0 mol/L to 6.0 mol/L, the diammonium hydrogenphosphate concentration ranges from 0.05 mol/L to 0.2 mol/L; and theurea concentration ranges from 0.01 mol/L to 1.0 mol/L.
 3. The methodaccording to claim 1, wherein the aqueous electrolyte bath has a pHvalue ranging from 10.3 to 11.6 and a temperature ranging from 18° C. to22° C.
 4. The method according to claim 1, wherein the current densityis at least 1 A/dm².
 5. The method according to claim 1, wherein thecurrent density ranges from 1 A/dm² to 3 A/dm².
 6. The method accordingto claim 1, further comprising electrically insulating areas of asurface of the implant which are not to be coated such that a coating ofthe ceramic layer is selectively applied to the implant.
 7. The methodaccording to claim 6, wherein electrically insulating the areas whichare not to be coated is achieved by applying a lacquer, film, or foil tothe areas of the surface of the implant which are not to be coated priorto immersing the implant into said aqueous electrolyte bath.